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immune signature

Ramin Radpour, Carsten Riether, Cedric Simillion, Sabine Höpner, Rémy Bruggmann, Adrian F Ochsenbein
CD8+ T cell immunosurveillance is crucial in solid tumors and T cell dysfunction leads to tumor progression. In contrast, the role of CD8+ T cells in the control of leukemia is less clear. We characterized the molecular signature of leukemia stem/progenitor cells (LSPCs) and paired CD8+ T cells in patients with acute myeloid leukemia (AML). Epigenetic alterations via histone deacetylation reduced the expression of immune-related genes in bone marrow (BM)-infiltrating CD8+ T cells. Surprisingly, a silenced gene expression pattern in CD8+ T cells significantly correlated with an improved prognosis...
March 15, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nannette Y Yount, David C Weaver, Ernest Y Lee, Michelle W Lee, Huiyuan Wang, Liana C Chan, Gerard C L Wong, Michael R Yeaman
Diversity of α-helical host defense peptides (αHDPs) contributes to immunity against a broad spectrum of pathogens via multiple functions. Thus, resolving common structure-function relationships among αHDPs is inherently difficult, even for artificial-intelligence-based methods that seek multifactorial trends rather than foundational principles. Here, bioinformatic and pattern recognition methods were applied to identify a unifying signature of eukaryotic αHDPs derived from amino acid sequence, biochemical, and three-dimensional properties of known αHDPs...
March 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
Larissa E Hillebrand, Thomas Reinheckel
Cancer cells within a tumor are heterogeneous and exist in a variety of functionally distinct cell states, which are thought to be hierarchically organized. The cell on top of this hierarchy, the cancer stem cell (CSC) or, alternatively, tumor initiating cell (TIC), is responsible for initiation, maintenance, progression, and relapse of tumors. For the execution of these functions, CSC are equipped with distinct molecular tools. Although proteolytic enzymes in cancers have been extensively studied in general, relatively few studies have addressed proteases in function and fate of CSC/TICs...
March 12, 2019: Biochimie
Saeid Parvandeh, Greg A Poland, Richard B Kennedy, Brett A McKinney
Vaccination is an effective prevention of influenza infection. However, certain individuals develop a lower antibody response after vaccination, which may lead to susceptibility to subsequent infection. An important challenge in human health is to find baseline gene signatures to help identify individuals who are at higher risk for infection despite influenza vaccination. We developed a multi-level machine learning strategy to build a predictive model of vaccine response using pre-vaccination antibody titers and network interactions between pre-vaccination gene expression levels...
March 14, 2019: Microorganisms
Solomon Antwi Boison, Bjarne Gjerde, Borghild Hillestad, Shokouh Makvandi-Nejad, Hooman K Moghadam
Amoebic gill disease (AGD) is one of the most important parasitic diseases of farmed Atlantic salmon. It is a source of major economic loss to the industry and poses significant threats to animal welfare. Previous studies have shown that resistance against this disease has a moderate, heritable genetic component, although the genes and the genetic pathways that contribute to this process have yet to be elucidated. In this study, to identify the genetic mechanisms of AGD resistance, we first investigated the molecular signatures of AGD infection in Atlantic salmon through a challenge model, where we compared the transcriptome profiles of the naïve and infected animals...
2019: Frontiers in Genetics
Lijun Liao, Kai Markus Schneider, Eric J C Galvez, Mick Frissen, Hanns-Ulrich Marschall, Huan Su, Maximilian Hatting, Annika Wahlström, Johannes Haybaeck, Philip Puchas, Antje Mohs, Jin Peng, Ina Bergheim, Anika Nier, Julia Hennings, Johanna Reißing, Henning W Zimmermann, Thomas Longerich, Till Strowig, Christian Liedtke, Francisco J Cubero, Christian Trautwein
OBJECTIVE: There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut-liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2-/- ) model resembling human primary sclerosing cholangitis (PSC). DESIGN: Male Mdr2 -/- , Mdr2-/- crossed with hepatocyte-specific deletion of caspase-8 ( Mdr2-/- /Casp8∆hepa ) and wild-type (WT) control mice were housed for 8 or 52 weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling...
March 14, 2019: Gut
Iris Helfrich, Bernhard B Singer
Malignant melanoma is the most aggressive and treatment resistant type of skin cancer. It is characterized by continuously rising incidence and high mortality rate due to its high metastatic potential. Various types of cell adhesion molecules have been implicated in tumor progression in melanoma. One of these, the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is a multi-functional receptor protein potentially expressed in epithelia, endothelia, and leukocytes. CEACAM1 often appears in four isoforms differing in the length of their extracellular and intracellular domains...
March 13, 2019: Cancers
Hongmei Fu, Maryam Jangani, Aleesha Parmar, Guosu Wang, David Coe, Sarah Spear, Inga Sandrock, Melania Capasso, Mark Coles, Georgina Cornish, Helena Helmby, Federica M Marelli-Berg
Protective immunity relies upon differentiation of T cells into the appropriate subtype required to clear infections and efficient effector T cell localization to antigen-rich tissue. Recent studies have highlighted the role played by subpopulations of tissue-resident memory (TRM ) T lymphocytes in the protection from invading pathogens. The intestinal mucosa and associated lymphoid tissue are densely populated by a variety of resident lymphocyte populations, including αβ and γδ CD8+ intraepithelial T lymphocytes (IELs) and CD4+ T cells...
2019: Frontiers in Immunology
Christin Lund-Andersen, Sigve Nakken, Ståle Nygård, Bastian Fromm, Lars Birger Aasheim, Ben Davidson, Lars Julsrud, Torveig Weum Abrahamsen, Annette Torgunrud Kristensen, Brit Dybdahl, Stein Gunnar Larsen, Eivind Hovig, Kjersti Flatmark
Peritoneal malignant mesothelioma is a rare disease with a generally poor prognosis and poor response to chemotherapy. To improve survival there is a need for increased molecular understanding of the disease, including chemotherapy sensitivity and resistance. We here present an unusual case concerning a young woman with extensive peritoneal mesothelioma who had a remarkable response to palliative chemotherapy (platinum/pemetrexed). Tumor samples collected at surgery before and after treatment were analyzed on the genomic and transcriptional levels (exome sequencing, RNA-seq and smallRNA-seq)...
March 12, 2019: Cold Spring Harbor Molecular Case Studies
Erika Van Nieuwenhove, Vasiliki Lagou, Lien Van Eyck, James Dooley, Ulrich Bodenhofer, Carlos Roca, Marijne Vandebergh, An Goris, Stéphanie Humblet-Baron, Carine Wouters, Adrian Liston
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common class of childhood rheumatic diseases, with distinct disease subsets that may have diverging pathophysiological origins. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. METHODS: Here we profiled the adaptive immune system of 85 patients with JIA and 43 age-matched controls with indepth flow cytometry and machine learning approaches...
March 12, 2019: Annals of the Rheumatic Diseases
C J Carter
Prenatal and early childhood infections have been implicated in autism. Many autism susceptibility genes (206 Autworks genes) are localised in the immune system and are related to immune/infection pathways. They are enriched in the host/pathogen interactomes of 18 separate microbes (bacteria/viruses and fungi) and to the genes regulated by bacterial toxins, mycotoxins and Toll-like receptor ligands. This enrichment was also observed for misregulated genes from a microarray study of leukocytes from autistic toddlers...
March 9, 2019: Neurochemistry International
Juan J Arroyo-Crespo, Ana Armiñán, David Charbonnier, Coralie Deladriere, Martina Palomino-Schätzlein, Rubén Lamas-Domingo, Jerónimo Forteza, Antonio Pineda-Lucena, María J Vicent
Triple-negative breast cancer (TNBC), an aggressive, metastatic, and recurrent breast cancer (BC) subtype, currently suffers from a lack of adequately described spontaneously metastatic preclinical models that faithfully reproduce the clinical scenario. We describe two preclinical spontaneously metastatic TNBC orthotopic murine models for the development of advanced therapeutics: an immunodeficient human MDA-MB-231-Luc model and an immunocompetent mouse 4T1 model. Furthermore, we provide a broad range of multifactorial analysis for both models that could provide relevant information for the development of new therapies and diagnostic tools...
March 12, 2019: International Journal of Cancer. Journal International du Cancer
Orla M Finucane, Jamie Sugrue, Ana Rubio-Araiz, Marie-Victoire Guillot-Sestier, Marina A Lynch
Inflammation and metabolism are intricately linked during inflammatory diseases in which activation of the nucleotide-binding domain-like receptors Family Pyrin Domain Containing 3 (NLRP3) inflammasome, an innate immune sensor, is critical. Several factors can activate the NLRP3 inflammasome, but the nature of the link between NLRP3 inflammasome activation and metabolism remains to be thoroughly explored. This study investigates whether the small molecule inhibitor of the NLRP3 inflammasome, MCC950, modulates the lipopolysaccharide (LPS) -and amyloid-β (Aβ)-induced metabolic phenotype and inflammatory signature in macrophages...
March 11, 2019: Scientific Reports
Pietro E Cippà, Jing Liu, Bo Sun, Sanjeev Kumar, Maarten Naesens, Andrew P McMahon
The mechanisms initiating late immune responses to an allograft are poorly understood. Here we show, via transcriptome analysis of serial protocol biopsies from kidney transplants, that the initial responses to kidney injury correlate with a late B lymphocyte signature relating to renal dysfunction and fibrosis. With a potential link between dysfunctional repair and immunoreactivity, we investigate the immunological consequences of dysfunctional repair examining chronic disease in mouse kidneys 18 months after a bilateral ischemia/reperfusion injury event...
March 11, 2019: Nature Communications
Bérénice A Benayoun, Elizabeth A Pollina, Param Priya Singh, Salah Mahmoudi, Itamar Harel, Kerriann M Casey, Ben W Dulken, Anshul Kundaje, Anne Brunet
Aging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here, we generated chromatin maps and transcriptomes from four tissues and one cell type from young, middle-aged, and old mice-yielding 143 high-quality data sets. We focused on chromatin marks linked to gene expression regulation and cell identity: histone H3 trimethylation at lysine 4 (H3K4me3), a mark enriched at promoters, and histone H3 acetylation at lysine 27 (H3K27ac), a mark enriched at active enhancers...
March 11, 2019: Genome Research
Taixian Li, Yanqiong Zhang, Rongtian Wang, Zhipeng Xue, Shangzhu Li, Yuju Cao, Daobing Liu, Yanfang Niu, Xia Mao, Xiaoyue Wang, Weijie Li, Qiuyan Guo, Minqun Guo, Na Lin, Weiheng Chen
Steroid-induced osteonecrosis of the femoral head (SONFH) is difficult to be diagnosed at the early stages when it can be administrated effectively. Yet, to date no study has been performed to identify diagnostic biomarkers and to develop diagnostic models for SONFH. In the current study, a total of 60 SONFH patients with Association Research Circulation Osseous (ARCO) stages I-IV, and 20 controls were enrolled and divided into the discovery and validation cohorts. The serum samples were collected and the gene expression profiles were detected by microarray analysis based on the discovery cohort...
March 7, 2019: Bone
Yi-Zhou Jiang, Ding Ma, Chen Suo, Jinxiu Shi, Mengzhu Xue, Xin Hu, Yi Xiao, Ke-Da Yu, Yi-Rong Liu, Ying Yu, Yuanting Zheng, Xiangnan Li, Chenhui Zhang, Pengchen Hu, Jing Zhang, Qi Hua, Jiyang Zhang, Wanwan Hou, Luyao Ren, Ding Bao, Bingying Li, Jingcheng Yang, Ling Yao, Wen-Jia Zuo, Shen Zhao, Yue Gong, Yi-Xing Ren, Ya-Xin Zhao, Yun-Song Yang, Zhenmin Niu, Zhi-Gang Cao, Daniel G Stover, Claire Verschraegen, Virginia Kaklamani, Anneleen Daemen, John R Benson, Kazuaki Takabe, Fan Bai, Da-Qiang Li, Peng Wang, Leming Shi, Wei Huang, Zhi-Ming Shao
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype...
February 19, 2019: Cancer Cell
Jaegil Kim, David Kwiatkowski, David J McConkey, Joshua J Meeks, Samuel S Freeman, Joaquim Bellmunt, Gad Getz, Seth P Lerner
Analysis of the IMvigor 210 trials involving patients with platinum-refractory or cisplatin-ineligible urothelial carcinoma who were treated with the PD-L1 inhibitor atezolizumab identified a resistance signature as an immune biomarker. Transcriptome profiling of 368 tumor samples from this trial revealed that the "genomically unstable" Lund subtype classification was associated with the best response. We developed and applied a novel single-patient subtype classifier based on The Cancer Genome Atlas 2017 expression-based molecular subtypes...
March 6, 2019: European Urology
Jessica J Chiang, Steve W Cole, Julienne E Bower, Michael R Irwin, Shelley E Taylor, Jesusa Arevalo, Andrew J Fuligni
BACKGROUND: Rates of depression increase and peak during late adolescence and alterations in immune processes are thought to be both a risk factor and outcome of depression. However, few studies have examined depression-immune dynamics among adolescents. Using a functional genomics approach, the current study examined whether depressive symptoms were associated with activation with a gene expression profile, characterized by upregulated expression of pro-inflammatory-related genes and downregulated expression of antiviral-related genes in a sample of older adolescents (Mage = 18...
March 6, 2019: Brain, Behavior, and Immunity
Mark E Snyder, Michael O Finlayson, Thomas J Connors, Pranay Dogra, Takashi Senda, Erin Bush, Dustin Carpenter, Charles Marboe, Luke Benvenuto, Lori Shah, Hilary Robbins, Jaime L Hook, Megan Sykes, Frank D'Ovidio, Matthew Bacchetta, Joshua R Sonett, David J Lederer, Selim Arcasoy, Peter A Sims, Donna L Farber
Tissue-resident memory T cells (TRM ) maintain immunity in diverse sites as determined in mouse models, whereas their establishment and role in human tissues have been difficult to assess. Here, we investigated human lung TRM generation, maintenance, and function in airway samples obtained longitudinally from human leukocyte antigen (HLA)-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, whereas lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo...
March 8, 2019: Science Immunology
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